This release from the Mayo Clinic describes the essentially negative results of a small, randomized and partly controlled trial of a widely used, but unproven treatment for arthritis. The treatment involves injecting a person’s own bone marrow containing pluripotent stem cells directly into arthritis-damaged knees. Popular in “regenerative medicine” clinics, Bone Marrow Aspirate Concentrate (BMAC) therapy, and a related therapy using Platelet Rich Plasma (PRP) from blood, cost many thousands of dollars and are not covered by insurance. BMAC therapy currently does not require FDA approval since many of its practitioners have argued successfully that harvesting cells from one’s own body and re-injecting them without complex processing does not constitute “a drug.” But neither has there been rigorous scientific testing for efficacy, adverse side effects, benefit compared with other treatments, and safety. The good news is that the Mayo Clinic study was designed to put some science behind a choice to use BMAC, which a few published articles conclude has helped many patients and for long periods of time.
The release notes that the study failed to make a scientific case that the therapy works to heal, cure or diminish osteoarthritic pain mainly because the 25 patients — each with two bad knees — served as their own controls for BMAC and it turns out that the “control” knees injected with plain saline benefited just as much as the stem cell treated knees.
Overall, the release uses weaselly language to give the stem cell treatment more benefit of the doubt than it deserves here, and devotes a lot of space making a case for the possibility that the injection of stem cells in one set of knees somehow “spread” systemically to the other knees. A meaningful discussion of harms and benefits are also missing.
Painful, debilitating osteoarthritis of the knees and other joints, especially in the elderly and in athletes, joggers, and sports enthusiasts, are a major cause of disability. Treatments with anti-inflammatories, steroids, surgery and painkillers all carry potential risks and the overall health care cost to individuals and society is significant. As the release notes, at least 600 stem cell clinics in the U.S. alone have offered at least one form of BMAC to more than 100,000 patients seeking cures or long-lasting pain-reducing treatment.
This study seeks to assess whether the use of a patient’s own bone marrow stem cells is a treatment for osteoarthritis, or arthritis of aging. This treatment and similar ones seek to find an option that is less invasive than surgery but more effective than existing treatments. The investigators report that both knees improved “dramatically,” but unexpectedly. The knee injected with the salt water solution did just as well as the knee injected with the active stem cell treatment.
In summary, the study is an important one in that it calls into question the unproven benefit of using a patient’s own bone marrow as a treatment for painful arthritis. Further studies should include double-blind design where one patient gets stem cells while another only gets the saline placebo.
The release notes that patients may pay “thousands” out of pocket. It could have offered some information on the cost of alternative therapies, which would have put the cost burden in context.
The release talks about “dramatic improvement” in the injected knees, but gives the reader no clue about what the baseline level of pain was, or how the improvement was measured. The investigators used a standard international measure of pain relief and function to score the patients before and after treatment. The release needed to describe the results more meaningfully. For example, it could have noted the range of improvement in the 25 patient volunteers.
It’s unclear why the release positioned this as a positive study suggesting that the treated knee got better. The problem is that the study design was testing to see if there was a difference between treatment and placebo — and there wasn’t. This means that the stem cell treatment was no better than the saline placebo, or a sham treatment. In claiming that the stem cell treatment was effective, the release quotes a study investigator saying that it is possible that the injection of stem cells into one knee resulted in benefit to the other.
No evidence is provided to support this hypothesis.
Descriptions of BMAC treatments note that there are minimal side effects, mostly pain at the injection site that lasts a few days and can be treated with painkillers. But there are potential short- and long-term complications (including infection) of bone marrow aspiration and injections into a joint which were not addressed.
The results were framed in a way that may lead readers to conclude that this was a positive study showing benefit from stem cell therapy when the opposite is in fact the case. The whole point of the study was to compare improvement in stem cell vs. placebo-treated knees. The fact that no difference was found means, quite simply, that there was no benefit for the stem cell treatment compared with a placebo. By failing to state this plain fact, the release demonstrates an inability to grasp the purpose of blinded, placebo-controlled research — which is necessary to distinguish between real, effective treatments and expensive scams. The release’s tortured attempts to find a silver lining in this study may have a harmful effect on readers.
No mongering here; this is a painful and widespread disorder. However, the severity of symptoms in this population were limited to those experiencing mild to moderate pain.
The release duly notes that funding was by the Mayo Clinic in Florida’s Center for Regenerative Medicine.
As noted earlier in this review, other treatments — tested and untested — exist, including Platelet Rich Plasma presumed to carry biological growth factors to arthritic joints; steroid injections; exercise; surgery; and analgesics. None were mentioned.
The release prominently notes the wide availability of regenerative medicine clinics and their offerings of BMAC for knees and other arthritic joints. And it makes clear that the results of this new small trial cannot underpin recommendations for its “routine” use. The release would have been stronger if it had explained what “non routine” use means in the context of the study’s findings.
We give them the benefit of the doubt here since the release reports on the meticulous stem cell count and the use of the patients’ own knees serving as both treatment recipients and controls. These are newsworthy parts of the study protocol. But the claim that it’s the “world’s first” probably should have been explained better or in the abscence of an explanation, avoided altogether.
The release in too many places hedges on affirmative conclusions and as such may leave the impression that there is evidence from this study to encourage patients to keep spending thousands on BMAC. The possibility that there was systemic spread of the BMAC to the saline-injected knee is speculative and remains a hypothesis.
This study showed no benefit. Indeed the knee that received the placebo treatment appeared to fare better, according to the study.